Tumor Treating Fields Therapy for Newly Diagnosed Glioblastoma

Abstract

A fundamental characteristic of glioblastomas is heterogeneity at the cellular and molecular levels between tumors as well as between individual cells within the tumor microenvironment. These inter-tumoral and intra-tumoral heterogeneities are what make glioblastomas so difficult to treat in patients. As the tumor progresses over time, it accumulates more alterations and co-opts normal physiological processes for growth and proliferation as well as evasion from the immune system. Tumor Treating Fields (TTFields), as delivered by the Optune device, interferes with the co-opted cell division machinery and potentiates anti-tumor immune response. The pre-specified interim analysis of the EF-14 randomized trial using the device in newly diagnosed glioblastoma patients was positive, and it has shown prolongation of both progression free survival and overall survival in patients received TTFields together with maintenance temozolomide when compared to those treated with temozolomide alone. The median progression free survival was 7.1 (95 % CI 5.9–8.2) months in the TTFields plus temozolomide cohort and 4.0 (95 % CI 3.3–5.2) months in the temozolomide alone cohort (hazard ratio = 0.62 [95 % CI 0.43–0.89], p = 0.001). The overall survival of the intent-to-treat population showed a median overall survival of 19.6 (95 % CI 16.6–24.4) months in the TTFields plus temozolomide group versus 16.6 (95 % CI 13.6–19.2) months in the temozolomide alone group (hazard ratio = 0.74, [95 % CI 0.56–0.98], p = 0.03). The combined treatment was well-tolerated and without unexpected side effects. Although results from additional outcome analyses will likely be reported in the future, the positive data from the interim analysis suggest that TTFields offer benefit to newly diagnosed patients with glioblastoma.